Cisternal and lumbar CSF levels of arachidonate metabolites after subarachnoid haemorrhage: An assessment of the biochemical hypothesis of vasospasm

Summary Several naturally occurring compounds have been identified in human cerebrospinal fluid (CSF) after subarachnoid haemorrhage (SAH) as possible vasoactive agents involved in the biochemical mechanism of vasospasm. The authors have measured, in 30 patients admitted for SAH, CSF concentrations of two arachidonic acid metabolites, Prostacyclin and Prostaglandin D₂, as representative of vasodilator and vasoconstrictor compounds. CSF samples were made available by lumbar punctures and intraoperative cisternal punctures. Nine patients presented with symptomatic vasospasm: lumbar CSF Prostaglandin D₂ levels are significantly higher than in patients without vasospasm. The Cisternal Prostaglandin D₂ level is significantly higher than the lumbar CSF concentration; CSF Prostacyclin levels do not significantly differ in the two groups of patients. These data suggest the presence of an imbalanced biochemical situation responsible for promoting vasospasm. The evaluation of cisternal levels of arachidonate metabolites support the hypothesis of the clotting phenomenon around the ruptured aneurysm wall as an important predictive pattern of vasospasm onset after SAH, as shown in computed tomography.This research was supported by a grant of the Italian Department of Instruction, Rome, Italy, 1984 and by a grant of Regione Lombardia.     

Effect of experimental subarachnoid hemorrhage on CSF eicosanoids in the rat

A simple and inexpensive experimental model of subarachnoid hemorrhage (SAH) was developed in the rat. Based on accumulating data indicating the important role of arachidonic acid metabolites in the etiology of delayed cerebral vasospasm, we investigated changes induced by SAH on cerebrospinal fluid (CSF) levels of prostaglandin E2 (PGE2), F2 alpha (PGF2 alpha), and thromboxane B2 (TXB2). SAH was produced by the cisternal injection of blood via percutaneous suboccipital puncture. SAH rats (n = 200) were injected with 300 microliters of fresh autologous arterial blood; Control rats (n = 100) received the same volume of mock CSF. In 60 additional animals, no injections were made. To follow the changes induced by SAH on both the spectrum and time course of CSF eicosanoids, cisternal CSF samples were collected under basal conditions, 6, 12, and 36 after cisternal injection. PGE2, PGF2 alpha, and TXB2 were assayed in aliquots of CSF obtained by pooling samples from each experimental group. Eicosanoids were assayed using radioimmunoassay techniques. Arterial spasm was verified in parallel groups of SAH and control rats by comparison of the angiographic diameters of the basilar arteries (BA) and middle cerebral arteries (MCA) to that of the stapedial artery. CSF levels of all three eicosanoids were significantly higher in the SAH groups compared to both noninjected and mock-CSF injected control rats. These increases in concentrations of eicosanoids were accompanied by a decrease in the mean vascular diameter (77.5-82.0% of control) on day 2 following cisternal injection. We conclude that marked elevations of spasmogenic eicosanoids in the CSF are associated with experimental SAH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cisternal and lumbar CSF concentration of arachidonate metabolites in vasospasm following subarachnoid hemorrhage from ruptured aneurysm: biochemical and clinical considerations

Two representative cases of subarachnoid hemorrhage in which prostaglandin D2 (PGD2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), stable metabolite of prostacyclin (PGI2), were monitored with serial lumbar punctures and detected in cisternal CSF during operations for aneurysm, are reported. In the case with demonstrated arterial vasospasm, prostaglandin D2 has a concentration trend with characteristic peak related to vasospasm; the synthesis of prostacyclin appears inhibited after the hemorrhage. In the patient without radiologic evidence of vasospasm, arachidonate metabolite concentration trend appears in a steady-state. Cisternal prostaglandin D2 concentration in the patient with demonstrated vasospasm is two times the highest lumbar CSF concentration, while 6-keto-prostaglandin F1 alpha concentration is very low. This suggests the role of the clotting phenomenon and likely confirms the importance of arachidonate metabolites in the genesis of cerebral arterial spasm following subarachnoid hemorrhage.     

Platelet derived growth factor and subarachnoid haemorrage: A study on cisternal cerebrospinal fluid

Summary Platelet derived growth factor (PDGF) was identified as a powerful mitogenic growth factor which is released from activated platelets and has a marked activity as vasoconstrictor agent. In the present study we have measured cisternal cerebrospinal fluid (CSF) levels of PDGF in 72 patients operated on for intracranial aneurysm in order to verify whether it might be related to the clinical aspects of SAH with special regard to symptomatic vasospasm.CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern the nearest to the aneurysm before aneurysm isolation and exclusion. The specimen were frozen in liquid nitrogen and stored at-80 ° C until analysis. PDGF was measured using a commercially available reagent. Values are expressed as pg/ml of CSF.In 18 cases no radiological and clinical signs of SAH were detected and the mean cisternal CSF level of PDGF was 885.0±104.5 pg/ml; 20 patients were operated on between day 1 and 3 from the last SAH episode: mean cisternal CSF level of PDGF was 1917.5±459.4 pg/ml. In 34 patients treated with delayed surgery protocol, mean cisternal CSF level of PDGF was 995.3±73.8 pg/ml. Statistical analysis showed significant differences between groups (P: 0.011). In the subgroup of patients operated on within day 3 after SAH, 6 presented vasospasm and had mean cisternal CSF PDGF level which was significantly higher (P<0.01) than in 14 patients without vasospasm. In the delayed surgical patients there was no significant difference in cisternal CSF levels of PDGF considering the occurrence of vasospasm.The results of the present study suggest that (a) after SAH there is a significant release of PDGF early after SAH and (b) higher levels of PDGF found in cisternal CSF of patients operated on within 72 hours after SAH may be predictive of symptomatic vasospasm.     

Increased levels of lipid peroxides as predictive of symptomatic vasospasm and poor outcome after aneurysmal subarachnoid hemorrhage

OBJECT: Cerebral vasospasm remains a devastating medical complication of aneurysmal subarachnoid hemorrhage (SAH). Reactive oxygen species and subsequent lipid peroxidation are reported to participate in the causes of cerebral vasospasm. This clinical study was performed to investigate the relationships between levels of lipid peroxides in cerebrospinal fluid (CSF) and both delayed cerebral vasospasm and clinical outcome after SAH. METHODS: Levels of phosphatidylcholine hydroperoxide (PCOOH) and cholesteryl ester hydroperoxide (CEOOH) in the CSF were measured in 20 patients with aneurysmal SAH. The patients' CSF was collected within 48 hours of hemorrhage onset and on Day 6 or 7 post-SAH. On Day 7, angiography was performed to verify the degree and extent of the vasospasm. The relationship between the patients' clinical profiles and the levels of lipid peroxides in the CSF were investigated. Both PCOOH and CEOOH were detectable in CSF, and their levels decreased within 7 days after onset of SAH. The levels of CEOOH within 48 hours after onset of hemorrhage were significantly higher in patients in whom symptomatic vasospasm later developed than in patients in whom symptomatic vasospasm did not develop (p = 0.002). Levels of PCOOH measured within 48 hours after onset of hemorrhage were significantly higher in patients with poor outcomes than in patients with good outcomes (p = 0.043). CONCLUSIONS: Increased levels of lipid peroxides measured in the CSF during the acute stage of SAH were predictive of both symptomatic vasospasm and poor outcome. Measurements of lipid peroxides in the CSF may be useful prognostically for patient outcomes as well as for predicting symptomatic vasospasm.     

Superoxide dismutase activity in cisternal cerebrospinal fluid after aneurysmal subarachnoid haemorrhage

Summary It has been recognised that the level of superoxide dismutase (SOD) significantly increases in CSF as the result of cerebral ischaemic damage. The aim of this study was to correlate the CSF levels of SOD enzymatic activity to the patterns of subarachnoid haemorrhage with regards to ischaemic complications due to vasospasm.A series of 78 patients operated on for intracranial aneurysms was studied; all patients were monitored with serial TCD measurements every second day after SAH. CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern nearest to the aneurysm. SOD activity was assayed spectrophotometrically.Mean cisternal CSF level of SOD in 12 control cases (12.99±2.33 U/ml) is significantly higher (p < 0.01) than in 26 patients operated on between day 1 and 3 from last SAH episode (4.44±0.7 U/ml) and in 40 patients treated by delayed surgery (7.64±0.92 U/ml). In 13 patients presenting neurological deterioration related to arterial vasospasm mean cisternal SOD level was 12.23±1.86 U/ml; in 27 cases without vasospasm mean level was 5.43±0.7 U/ml (p < 001).The present results suggest that (a) cisternal CSF levels of SOD significantly decreases after SAH, probably in relation to an impaired synthesis in the brain compartment and that (b) a substantial elevation of SOD levels is evident in patients suffering ischaemic complications vasospasm-related. Biochemical events in the brain compartment could influence the expression and release of anti-oxidant enzymes in CSF after SAH.     

The effect of continuous drainage of cerebrospinal fluid in patients with subarachnoid hemorrhage: a retrospective analysis of 108 patients

The effects of continuous drainage of cerebrospinal fluid (CSF) on vasospasm and hydrocephalus were analyzed retrospectively in 108 patients with subarachnoid hemorrhage (SAH) who were operated on for ruptured aneurysms within 48 hours of their onset. Ninety-two of these patients underwent a procedure for CSF drainage (cisternal drainage, ventricular drainage, lumbar drainage, or a combination of these). The duration, the total volume, and the average daily volume of CSF drainage were 10.4 +/- 7.0 days (mean +/- SD). 2034 +/- 1566 ml, and 190 +/- 65.3 ml, respectively. Patients with a greater drainage volume at a lower height of drainage in the early period after SAH developed more cerebral infarctions later (P less than 0.025). The relationship between the total volume of CSF removed and shunt-dependent hydrocephalus was determined to be statistically significant (P less than 0.005). Cerebral infarction and hydrocephalus after SAH were also found to be statistically associated (P less than 0.001). Thus, continuous cerebrospinal fluid drainage should not be performed too readily in patients with SAH, because the removal of a large amount of CSF can induce cerebral vasospasm as well as hydrocephalus.     

Neuropeptide Y in the primate model of subarachnoid hemorrhage.

The cause of cerebral vasospasm after subarachnoid hemorrhage (SAH) remains unknown. Recently, an association between the potent vasoconstricting peptide, neuropeptide Y, and delayed cerebral vasospasm after SAH has been postulated. This was based on the findings of increased neuropeptide Y levels in the cerebrospinal fluid (CSF) and plasma after SAH in animals and humans. For this study, the primate model of SAH was used to assess the possible role of neuropeptide Y in delayed vasospasm after SAH. Fifteen cynomolgus monkeys underwent placement of a clot of either whole blood or red blood cells in the subarachnoid space around the middle cerebral artery (MCA). Sequential arteriography for assessment of MCA diameter and sampling of blood and CSF for neuropeptide Y were performed: before SAH (Day 0); 7 days after SAH, when signs of delayed cerebral vasospasm peak in this model and in humans; 12 days after SAH; and 28 days after SAH. Subarachnoid hemorrhage did not evoke changes in CSF or plasma levels of neuropeptide Y. Nine monkeys had arteriographic evidence of vasospasm on Day 7, but no change in neuropeptide Y levels occurred in plasma or CSF. In addition, neuropeptide Y levels did not change, even after resolution of vasospasm on Day 12 or Day 28. Neuropeptide Y levels were substantially higher in CSF than in arterial plasma (p less than 0.003 at each interval). No correlation was found between neuropeptide Y levels in CSF and in plasma. These results do not confirm a relationship between neuropeptide Y levels in the CSF or peripheral plasma and delayed cerebral vasospasm in SAH.     

Effect of leukotriene antagonist on experimental delayed cerebral vasospasm.

Experimental delayed cerebral vasospasm was produced in 16 adult mongrel dogs by the "two-hemorrhage" method of intracisternal injections of autologous arterial blood. Group 1 was a control group. Group 2 was a treatment group that received an intravenous injection of ONO-1078, a novel potent leukotriene antagonist, once a day for 7 days just after the first cisternal injection of the blood. Angiography was performed on Days 0 and 7, and the cerebrospinal fluid levels of leukotriene C4 (LTC4) were measured on Days 0, 3, and 7. The cisternal levels of LTC4 increased after subarachnoid hemorrhage in both groups. But the cerebrospinal fluid levels of LTC4 in the treatment group were significantly lower than those in the control group (P less than 0.05). The angiographic vasospasm after subarachnoid hemorrhage was partially prevented with the treatment of intravenous injections of ONO-1078 (P less than 0.001). These results suggest that LTC4 may play a role in the pathogenesis of delayed cerebral vasospasm, directly or indirectly, and ONO-1078 may have a therapeutic effect on the prevention of the development of delayed cerebral vasospasm.     

Enhanced cisternal drainage and cerebral vasospasm in early aneurysm surgery

Summary Enhanced cisternal drainage was performed following early aneurysm surgery in patients with Hunt and Kosnik grades I–III, to effect continuous wash-out of subarachnoid blood clots and reduce symptomatic vasospasm. Following extensive evacuation of the cisternal blood clots, the Liliequist's membrane was opened extensively and a third ventriculostomy was effected by opening the lamina terminals. The drainage effect was considered as poor, moderate or fair, depending on the average amount of CSF drainage/day. SAH was graded into 0–III depending on the severity of cisternal haematoma in the pre-operative CT. No symptomatic vasospasm occurred in patients with SAH grade I. In SAH grade II +III patients symptomatic vasospasm occurred in 78,60 and 42% of patients with a poor, moderate and fair drainage effect, respectively. Nine patients who developed symptomatic vasospasm were treated by hypertensive/hypervolemic therapy (HHT). The HHT was effective in 7 patients with fair and moderate CSF drainage and ineffective in 2 patients with poor a drainage effect. It seems, that enhanced post-operative cisternal drainage can reduce the incidence of symptomatic vasospasm and be of benefit to the outcome of early aneurysm surgery.     

Prevention of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage by intraoperative cisternal fibrinolysis using tissue-type plasminogen activator combined with continuous cisternal drainage

The efficacy of intraoperative cisternal irrigation using tissue-type plasminogen activator (tPA) combined with continuous cisternal drainage was assessed for the prevention of symptomatic vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). Seventy consecutive patients underwent direct surgery for aneurysm clipping within 48 hours of SAH and had computed tomography (CT) findings classified as Fisher group III or IV with densities of more than 65 Hounsfield units (HU). Fibrinolysis of the cisternal clots was performed during surgery using 1.6 mg tPA in 55 cases or 3.2 mg tPA in 15 cases. If postoperative CT within 24 hours of surgery showed areas with density more than 65 HU, additional tPA (0.8 mg/day) was administered into the cisternal catheter until the high density areas disappeared. The cisternal drainage catheters were left in place until day 14. Additional tPA injection was necessary in four of the 55 patients receiving 1.6 mg tPA. Symptomatic vasospasm occurred in three patients (4.3%) and two patients had low density areas on CT. Permanent deficit (hemiparesis) due to cerebral vasospasm remained in only one patient. Intraoperative cisternal irrigation with tPA combined with cisternal drainage is safe and effective for the prevention of symptomatic vasospasm following SAH.     

Influence of blood volume on cerebrospinal fluid levels of arachidonic acid metabolites after subarachnoid hemorrhage: experimental study on the pathogenesis of cerebral vasospasm

Based on accumulating data indicating the important role of arachidonic acid metabolites in the pathogenesis of cerebral vasospasm, we examined the influence of alterations in blood volume on the cerebrospinal fluid (CSF) level of the subarachnoid hemorrhage (SAH). Three separate injections of autologous blood into the cisterna magna of dogs within subarachnoid hemorrhage (SAH). Three separate injections of autologous blood into the cisterna magna of dogs within 72 hours were performed. Three experimental groups were formed, with an overall injected blood volume of 6, 9, and 12 ml. Arterial spasm was verified by comparison of the angiographic diameter of the basilar artery on Day 8 vs. Day 1. Additionally, light microscopic, scanning and transmission electron microscopic, and freeze cracking technique examinations of the basilar artery demonstrated the typical morphological features of proliferative vasculopathy. Increasing the volume of experimental SAH led to a linear decrease of the mean vessel diameter from 45% to 53% and finally to 75% of normal. Parallel to the reduction of angiographic vessel lumen, a volume-dependent significant increase of all three eicosanoids was demonstrated. A deficiency of prostacyclin concentration during the course of the experiment was not observed. Despite highly elevated CSF levels of vasodilating prostacyclin, however, severe angiographic constriction of the basilar artery occurred in the presence of high concentrations of TXA2 and PGE2. It is concluded that increasing volumes of SAH led to a concomitant release of arachidonic acid metabolites during posthemorrhagic clot lysis. From our data, it seems questionable whether a prostacyclin deficiency is an important underlying factor for the development of cerebral spasm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rapid Induction of Meningeal Collagen Synthesis in the Cerebral Cisternal and Ventricular Compartments after Subarachnoid Hemorrhage

Summary. Procollagen propeptides in the lumbar CSF increase after subarachnoid hemorrhage (SAH), and elevated concentrations have been detected as early as on day 8. We studied here the timing and localization of the induction of meningeal collagen synthesis during the first week after SAH by analysing cisternal and ventricular CSF samples. We obtained 29 cisternal and 10 ventricular CSF samples at operation from patients with SAH between days 1 and 9 after onset. The carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured using radio-immunoassays. The concentrations of PICP and PIIINP in the cisternal CSF were elevated as early as on day 2 after SAH. PICP increased in a sigmoidal fashion (R²=0.39, p<0.001), while PIIINP increased linearly (R²=0.28, p=0.003) and was approximately 3-fold higher on day 9 than initially. PICP was twice as high (p=0.02) in the cisternal than in the ventricular CSF after SAH and PIIINP was 4-times higher (p=0.007). Interestingly, the concentrations were similar in a patient with intraventricular bleeding. The cisternal compartment contributed to the propeptides in the CSF more than did the ventricular compartment, but the latter also appeared to have a definite potential for fibroproliferative reaction. Meningeal collagen synthesis was induced rapidly within the first few days after SAH suggesting that therapeutic attempts to inhibit the fibroproliferative reaction should be started as early as possible.     

Marked reduction of cerebral vasospasm with lumbar drainage of cerebrospinal fluid after subarachnoid hemorrhage

OBJECT: Cerebral vasospasm after subarachnoid hemorrhage (SAH) continues to be a major source of morbidity in patients despite significant clinical and basic science research. Efforts to prevent vasospasm by removing spasmogens from the subarachnoid space have produced mixed results. The authors hypothesize that lumbar cisternal drainage can remove blood from the basal subarachnoid spaces more effectively than an external ventricular drain (EVD). This non-randomized, controlled-cohort study was undertaken to evaluate the effectiveness of a lumbar drain in patients with SAH compared with those in whom an EVD or no form of cerebrospinal fluid (CSF) drainage was used to prevent the development of clinical vasospasm and its sequelae. METHODS: The authors collected data on 266 patients with nontraumatic SAH who were admitted to the University of Utah Health Sciences Center between January 1994 and January 2003. Of these, 167 met the study entry criteria. The treatment group consisted of 81 patients in whom a lumbar drain had been placed for CSF shunting, whereas the control group was composed of 86 patients who received no form of CSF drainage or who were treated solely with an EVD. Primary outcome measures were as follows: 1) clinically evident vasospasm; 2) the need for endovascular intervention; 3) vasospasm-induced infarction; 4) disposition at time of discharge; and 5) Glasgow Outcome Scale (GOS) score at 1 to 3 months postdischarge. Secondary outcomes included length of stay and the need for CSF shunting. The presence of a lumbar drain conferred a statistically significant protective and beneficial effect across all outcome measures, reducing the incidence of clinical vasospasm from 51 to 17%, the need for angioplasty from 45 to 17%, and the occurrence of vasospastic infarction from 27 to 7% (all p < or = 0.001-0.008). Patients in the treatment group were more likely to be discharged home (54% compared with 25%, p = 0.002) and to have a GOS score of 5 at follow up (71% compared with 35%, p < 0.001). The mean number of days spent in the intensive care unit and in the hospital overall was also fewer in the treatment group. A similar degree of benefit was found in patients with different Fisher grades and regardless of whether an EVD was needed on presentation, both by subgroup analysis and multivariate logistic regression modeling. There was no statistical difference between the groups in terms of patients requiring a shunt. Complications with lumbar drains were rare and yielded no permanent sequelae. CONCLUSIONS: Shunting of CSF through a lumbar drain after an SAH markedly reduces the risk of clinically evident vasospasm and its sequelae, shortens hospital stay, and improves outcome. Its beneficial effects are probably mediated through the removal of spasmogens that exist in the CSF. The results of this study warrant a randomized clinical trial, which is currently under way.     

Effects of intravascular volume expansion on cerebral blood flow in patients with ruptured cerebral aneurysms

To clarify the effect of intravascular volume expansion on cerebral blood flow (CBF) in patients after subarachnoid hemorrhage (SAH), we performed 55 pairs of regional CBF measurements using the xenon-133 inhalation method before and after volume expansion in 35 patients with ruptured cerebral aneurysms. CBF was calculated as the hemispheric mean value of the initial slope index. To accomplish volume expansion, we transfused 500 ml of 5% human serum albumin in half an hour. After volume expansion with albumin, the hemoglobin value decreased significantly (P less than 0.005). Volume expansion did not change the mean arterial blood pressure. During the first 2 weeks after SAH, CBF decreased significantly after volume expansion (P less than 0.005). During the 3rd week after SAH and subsequently to the 4th week after SAH, volume expansion produced no change in CBF. In patients with symptomatic vasospasm, CBF decreased significantly after volume expansion (P less than 0.005). In patients without symptomatic vasospasm, volume expansion produced no change in CBF. The results of this study suggest that increasing the intravascular volume above normal by volume expansion does not increase CBF or reverse symptomatic vasospasm.     

Delayed CSF lavage for arteriographic and morphological vasospasm after experimental SAH

Irrigation of the subarachnoid space after aneurysmal subarachnoid hemorrhage (SAH) has been reported to alleviate subsequent arterial vasospasm. The authors have investigated the effect of lavage of the cerebrospinal fluid (CSF) space in the two-hemorrhage canine model of vasospasm. Twelve dogs had basilar cistern lavage with 120 cc of artificial CSF 24 hours after each of two SAH's, and 12 control dogs had two sequential SAH's without intervening lavage of clot. The amount of clot on the ventral brain stem was evaluated at sacrifice and was graded from 0 (no clot) to 4 (maximum clot) to assess the adequacy of clot removal. Dogs that had undergone lavage had a median grade of 1 (range Grade 0 to 2); control dogs had a median grade of 2 (range Grade 1 to 3.5, p less than 0.001. Wilcoxon rank sum test), indicating significant reduction of gross clot by lavage. The neurological findings were graded from 0 to 5, based on meningismus, ataxia, paresis, and cranial nerve deficits. No significant differences in neurological grade were found on any day between the two groups. Satisfactory angiograms were obtained before and 7 days after hemorrhage and were controlled for blood pressure and blood gases; these showed significant spasm in both groups. There was a mean reduction (+/- standard deviation) of 21.6% +/- 16.2% in basilar artery diameter in control dogs, compared to a 28.8% +/- 15.1% reduction in dogs with lavage (difference not significant, t-test). There was a strong, but insignificant, trend toward reduction of endothelial desquamation in the basilar and middle cerebral arteries in dogs with lavage compared to control animals (p = 0.06). Corrugation and tearing of the elastica, thickened intima, intimal fibroplasia, vacuolization of the endothelial or smooth-muscle cells, and presence of blood cells in the adventitia occurred similarly in both groups. It appears that cisternal lavage 24 hours after hemorrhage in this model has no effect on the angiographic, neurological, or most morphological sequelae of SAH, in spite of evidence for removal of clot as seen at sacrifice. Any postulated interaction of clot and vessel resulting in chronic vasospasm must occur before this time. Evaluation of the effect of much earlier lavage (for instance, 1 hour after hemorrhage) may elucidate the point at which vasospasm is instigated after SAH, and help in determining what factors cause vasospasm.     

Regional CBF, intraventricular pressure, and cerebral metabolism in patients with ruptured intracranial aneurysms

Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (CMRO2), intraventricular pressure, and lactate/pH levels in the cerebrospinal fluid (CSF) were measured in 38 patients with ruptured intracranial aneurysms between the 3rd and 13th day after subarachnoid hemorrhage (SAH). Angiography was performed following the rCBF study and the degree of vasospasm was measured on the angiograms. The patients were graded clinically according to the system of Hunt and Hess. Cerebral vasospasm significantly influenced rCBF: global reductions and focal changes (ischemia, hyperemia, and tissue peaks) were commonly associated with vasospasm. Patients with severe diffuse spasm always had global ischemia (21 +/- 5 ml/100 gm/min), and cerebral infarctions were demonstrated subsequently, The CMRO2 was more reduced than rCBF, indicating an uncoupling between flow and metabolism. This relative luxury perfusion was associated with CSF lactic acidosis and intracranial hypertension. The arteriovenous difference of oxygen was equally reduced in all categories of patients, probably due to the primary insult of SAH. The CMRO2 decreased concomitantly with arterial caliber, indicating a secondary impairment of cerebral metabolism due to vasospasm.     

Changes of endothelin concentration in cerebrospinal fluid and plasma of patients with aneurysmal subarachnoid hemorrhage

To investigate the clinical significance of endothelin (ET), a potent vasoconstrictor peptide, in subarachnoid hemorrhage (SAH) and SAH-related cerebral vasospasm, we measured the ET-like immunoreactivity (ETLI) in plasma and cerebrospinal fluid (CSF) obtained serially from patients with SAH due to ruptured cerebral aneurysm who underwent aneurysmal surgery. The normal ET–LI levels in plasma and CSF (n = 24) were 12.4±2.0 (mean±s.d.) and 9.1±1.2 pg·ml^-1, respectively. Plasma ET-LI levels in patients with SAH before surgery (16.8±7.8 pg·ml^-1, n = 8) were higher than the normal values ( P <0.05), and became further elevated after surgery (22.5±9.4 pg·ml^-1). ET-LI levels in plasma and CSF one day after surgery were 18.7±5.5 and 18.4±6.8 pg·ml^-1 ( P <0.01 vs. normal values), respectively, and declined thereafter. The plasma and CSF ET-LI levels in patients who showed symptomatic vasospasm became concomitantly elevated again. These results suggest that ET is involved in SAH-related vasospasm and raise the possibility that surgical stress influences the vasospasm.     

Effectiveness of the head-shaking method combined with cisternal irrigation with urokinase in preventing cerebral vasospasm after subarachnoid hemorrhage

OBJECT: The head-shaking method combined with cisternal irrigation has been proposed to be effective in preventing cerebral vasospasm after subarachnoid hemorrhage (SAH) by facilitating rapid washout of the clot from the subarachnoid space. This study was conducted to evaluate the effectiveness of this method. METHODS: The inclusion criteria included the following: 1) Fisher Grade 3 SAH on admission computerized tomography (CT) scans; 2) aneurysm secured within 48 hours of SAH onset; and 3) no focal deficit and ability to obey commands within 24 hours postsurgery. Two hundred thirty patients treated between 1994 and 2002 fulfilled the criteria. Because only one machine was available and it required I month of maintenance every other month, 114 patients underwent irrigation combined with the head-shaking method (head-shaking group), whereas the remaining 116 patients received cisternal irrigation alone (control group). There were no significant differences in sex, age, site of aneurysm, or preoperative grade between the two groups. The incidence of symptomatic vasospasm with or without infarction, cerebral infarction on CT scans, and permanent ischemic neurological deficit was 25.7, 17.7, and 8.8%, respectively, in the control group and 15.2, 4.5, and 2.7% in the head-shaking group. The difference was statistically significant for symptomatic vasospasm, cerebral infarction, and permanent ischemic neurological deficit (p < 0.05). In a multivariate backward stepwise logistic regression analysis, absence of head shaking was the only variable that was predictive of permanent ischemic neurological deficit (p = 0.061). The outcomes evaluated using the modified Rankin Scale were better in the head-shaking group (p = 0.051). CONCLUSIONS: The head-shaking method significantly reduced the incidence of symptomatic vasospasm, cerebral infarction, and permanent ischemic neurological deficit and improved the clinical outcomes in patients who underwent cisternal irrigation therapy after aneurysmal SAH.     

The role of endothelin-1 in the origin of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

Plasma and cerebrospinal fluid (CSF) endothelin (ET)-1-like immunoactivity in 27 patients with aneurysmal subarachnoid hemorrhage (SAH) was measured serially by radioimmunoassay for 2 weeks after SAH onset. Mean ET-1-like immunoactivity levels in plasma of patients with SAH were highly elevated during the whole study period, while the levels in CSF of the same patients were not. Plasma ET-1-like immunoactivity levels in patients with SAH classified as Fisher computerized tomography (CT) Group 3 were higher than those in patients with SAH classified as Fisher CT Groups 1 and 2. There were no significant differences in plasma ET-1-like immunoactivity levels between the patient groups stratified by Hunt and Kosnik grade. In this series, plasma ET-1-like immunoactivity levels in the 12 patients with vasospasm were higher than those in the 15 patients without vasospasm during the 1st week; CSF ET-1-like immunoactivity levels in patients with vasospasm were in the normal range on Days 0 to 3 after SAH onset, then became elevated on Days 5 to 7 and remained high until the end of the 2nd week. In contrast, CSF ET-1-like immunoactivity levels in patients without vasospasm were within the normal range during the entire period of study. The time course of the occurrence of vasospasm and that of the increase in CSF ET-1-like immunoactivity coincided precisely. The possible role of endogenous ET-1 in the pathogenesis of vasospasm due to SAH is discussed.